Linking Parkinson’s disease and Alzheimer’s disease: A Mendelian Randomization Study on Causal Relationships and Clinical Implications

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Abstract Parkinson's Disease and Alzheimer's Disease are the two most common neurodegenerative conditions. Contemporary research has unraveled distinct key mechanisms that account for two diseases, although disturbance of pathways that responsible for Parkinson's Disease has been found to be implicated in Alzheimer's Disease, and vice versa. In order to investigate if there is causal relationship between these two intertwined diseases, we conducted a two-sample Mendelian randomisation analysis encompassing 482,730 PD individuals and 218,792 AD individuals. Using SNPs from publicly available genome-wide association study datasets, we chose instrumental variables for a two-sample MR analysis while adhering to important Mendelian randomisation assumptions. The primary analysis using the Inverse Variance Weighted method indicated a significant causal effect of Parkinson's Disease on Alzheimer's Disease (OR = 1.071766, 95% CI: 1.0062448, 1.141554; p = 0.03218492). The IVW analysis tested the bi-directional relationship between Alzheimer's disease (finn-b-G6_ALZHEIMER) and Parkinson's disease (ieu-b-7), with no significant evidence suggesting reverse causation. Sensitivity analyses, including heterogeneity tests, MR-Egger regression, leave-one-out, and reverse causation analysis, validated the robustness of the findings, showing no evidence of pleiotropy or. Clinically, these data suggest that Parkinson's Disease patients may benefit from early Alzheimer's Disease screening and interventions, which could improve individualized treatment approaches and public health initiatives. This study underlines the ability of genetic insights to influence integrated care approaches, ultimately improving patient outcomes with neurodegenerative diseases.

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